Efficacy and safety of polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin and prednisone for previously untreated diffuse large B-cell lymphoma: A real-world, multi-center, retrospective cohort study.

Abstract

7061 Background: In the POLARIX study, Pola-R-CHP showed significant improvement in progression free survival (PFS) in previously untreated DLBCL compared to R-CHOP. However, there are still few reports about the efficacy and safety of Pola-R-CHP in real-world setting in China, leaving some questions about the optimal patient population for Pola-R-CHP. Therefore, we conducted this retrospective observational study to compare the efficacy and safety of Pola-R-CHP with R-CHOP in clinical practice. Methods: The Pola-R-CHP group included previously untreated DLBCL patients who received Pola-R-CHP therapy across 6 medical centers in China. The control group included previously untreated DLBCL patients treated with R-CHOP. Patients treated with Pola-R-CHP were matched by propensity scores with those treated with R-CHOP. The primary endpoint was 12-month PFS based on Lugano 2014 criteria. Results: A total of 650 eligible patients from 6 centers were identified, 155 receiving Pola-R-CHP and 495 R-CHOP. After 1:2 propensity score matching, 150 pairs were obtained for further survival and prognosis analysis. With a median follow-up of 14.3 months, 12-month progression-free survival (PFS) was numerically higher with Pola-R-CHP versus R-CHOP (90.5% vs 84.8%, P=0.19). Benefits were consistently observed across molecular subgroups, especially advanced stage, ECOG≥2, extranodal involvement ≥2 and non-GCB group. The complete response rate of the Pola-R-CHP group was higher than that of the RCHOP group (87.2% vs 80.1%; P=0.11), but there was no statistical difference. Among 150 patients treated with Pola-R-CHP, 110 underwent gene sequencing analysis: MCD (25.5%), combined subtype (14.5%), ST2 (10.9%), and other/unclassifiable subtype (31.8%). The most common mutations (>25% of cases) were PIM1, TP53, BCL-6, KMT2D, SOCS1, BCL-2. Genetic testing results show the correlation between genotyping, gene mutations in PIM1/TP53 and therapeutic efficacy. Safety was comparable between Pola-R-CHP and R-CHOP, including rates of grade 3 to 4 AE. Prophylactic PEG-G-CSF administration was given in most of the cases. No deaths due to AE were observed. Unexpected adverse events were not observed. Conclusions: This large real-world study supports Pola-R-CHP as an effective frontline option for DLBCL, with sustained efficacy versus R-CHOP observed in unselected populations. While 12-month PFS failed to reach statistical significance, subgroup analyses favor Pola-R-CHP. Further research with a wider population, longer follow-up, and screening of advantageous groups are warranted.